干预载脂蛋白AⅠ表达的研究进展

The development of regulatory factors on apolipoprotein AⅠ expression

大量的临床流行病学研究已经表明,高密度脂蛋白(HDL)水平与心血管疾病风险呈负相关。载脂蛋白AⅠ(Apo AⅠ)是HDL中的主要功能蛋白,其含量约占HDL的70%左右。寡脂的Apo AⅠ是ATP结合盒转运子A1(ABCA1)介导的巨噬细胞胆固醇流出的主要接受体,能够介导巨噬细胞中游离胆固醇的外流,启动胆固醇逆转运(RCT)过程,并在肝外组织清除过多胆固醇。大量的动物实验也已证实即使HDL保持正常水平,Apo AⅠ的缺乏也可导致动脉粥样硬化病变加重,过表达人Apo AⅠ基因抑制动脉粥样硬化早期脂纹的产生,因此调控Apo AⅠ基因表达对动脉粥样化及其他心血管疾病具有重要意义。本文拟就干预Apo AⅠ基因表达调控机制及诱导和抑制Apo AⅠ表达的相关因素进行综述。

A large number of clinical epidemiological studies have shown that high density lipoprotein （HDL） level is inversely associated with cardiovascular disease risk factors. Apolipoprotein A Ⅰ（ApoA Ⅰ ） is the main functional protein in HDL, and the content of HDL is about 70%. Oligo-lipid ApoA Ⅰ is the main recipient of ATP-binding cassette transporters （ABCA1） mediated cholesterol efflux from macrophages. It can mediate cholesterol efflux free from macrophage, then start reverse cholesterol transport （RCT） process, and remove excess cholesterol in extrahepatic tissue. A large number of animal experiments have also confirmed that the lack of HDL ApoA Ⅰ can also lead to the increase of atherosclerosis, and overexpression of human ApoA Ⅰ gene can significantly inhibit the generation of early atherosclerosis in mice. The mechanisms of ApoA Ⅰ gene expression and the related factors of inducing and inhibiting ApoA Ⅰ expression will be reviewed in this article.